A novel form of recessive limb girdle muscular dystrophy with mental retardation and abnormal expression of alpha-dystroglycan

Cataloged from PDF version of article.The limb girdle muscular dystrophies are a heterogeneous group of conditions characterized by proximal muscle weakness and disease onset ranging from infancy to adulthood. We report here eight patients from seven unrelated families affected by a novel and relatively mild form of autosomal recessive limb girdle muscular dystrophy (LGMD2) with onset in the first decade of life and characterized by severe mental retardation but normal brain imaging. Immunocytochemical studies revealed a significant selective reduction of α-dystroglycan expression in the muscle biopsies. Linkage analysis excluded known loci for both limb girdle muscular dystrophy and congenital muscular dystrophies in the consanguineous families. We consider that this represents a novel form of muscular dystrophy with associated brain involvement. The biochemical studies suggest that it may belong to the growing number of muscular dystrophies with abnormal expression of α-dystroglycan. © 2003 Published by Elsevier B.V

In vitro antimicrobial effects of aztreonam, colistin, and the 3-drug combination of aztreonam, ceftazidime and amikacin on metallo-β-lactamase-producing Pseudomonas aeruginosa

<p>Abstract</p> <p>Background</p> <p>There are limited choice of antimicrobial agents to treat infection with metallo-<it>β</it>-lactamase-producing <it>Pseudomonas aeruginosa</it>. We evaluate the antimicrobial effects of aztreonam alone, colistin alone and the 3-drug combination of aztreonam, ceftazidime and amikacin on 23 strains of metallo-<it>β</it>-lactamase-producing <it>P. aeruginosa </it>by time-killing tests.</p> <p>Methods</p> <p>Strains used were from different hospitals in Japan and had different pulse-field gel electrophoresis patterns by restriction with <it>Spe</it>I. The minimum inhibitory concentrations of 11 antimicrobial agents (piperacillin, piperacillin/tazobactam, imipenem, meropenem, aztreonam, ceftazidime, amikacin, tobramycin, arbekacin, ciprofloxacin and colistin) were determined using the agar dilution test. The effects of aztreonam, colistin and the combination of aztreonam, ceftazidime and amikacin were determined by time-killing studies.</p> <p>Results</p> <p>Bacteriostatic effects after 6 hours of drug exposure were observed in 12 strains (52.2%) of 23 strains of metallo-<it>β</it>-lactamase-producing <it>P. aeruginosa </it>with 48 mg/l aztreonam, in 19 strains (82.6%) with the 3-drug combination of 16 mg/l aztreonam, 16 mg/l ceftazidime, and 4 mg/l amikacin, and in 23 strains (100%) with 2 mg/l colistin. Bactericidal effects after 6 h drug exposure were observed in 1 strain (4.3%) with 48 mg/l aztreonam, in 8 strains (30.4%) with the 3-drug combination and in all 23 strains (100%) with 2 mg/l colistin.</p> <p>Conclusion</p> <p>Evaluation of <it>in vitro </it>antimicrobial effects on metallo-<it>β</it>-lactamase-producing <it>P. aeruginosa </it>revealed relatively good effects of the 3-drug combination of aztreonam, ceftazidime and amikacin and marked effects of colistin.</p

Transcriptome Analysis of the Hippocampal CA1 Pyramidal Cell Region after Kainic Acid-Induced Status Epilepticus in Juvenile Rats

Molecular mechanisms involved in epileptogenesis in the developing brain remain poorly understood. The gene array approach could reveal some of the factors involved by allowing the identification of a broad scale of genes altered by seizures. In this study we used microarray analysis to reveal the gene expression profile of the laser microdissected hippocampal CA1 subregion one week after kainic acid (KA)-induced status epilepticus (SE) in 21-day-old rats, which are developmentally roughly comparable to juvenile children. The gene expression analysis with the Chipster software generated a total of 1592 differently expressed genes in the CA1 subregion of KA-treated rats compared to control rats. The KEGG database revealed that the identified genes were involved in pathways such as oxidative phosporylation (26 genes changed), and long-term potentiation (LTP; 18 genes changed). Also genes involved in Ca2+ homeostasis, gliosis, inflammation, and GABAergic transmission were altered. To validate the microarray results we further examined the protein expression for a subset of selected genes, glial fibrillary protein (GFAP), apolipoprotein E (apo E), cannabinoid type 1 receptor (CB1), Purkinje cell protein 4 (PEP-19), and interleukin 8 receptor (CXCR1), with immunohistochemistry, which confirmed the transcriptome results. Our results showed that SE resulted in no obvious CA1 neuronal loss, and alterations in the expression pattern of several genes during the early epileptogenic phase were comparable to previous gene expression studies of the adult hippocampus of both experimental epileptic animals and patients with temporal lobe epilepsy (TLE). However, some changes seem to occur after SE specifically in the juvenile rat hippocampus. Insight of the SE-induced alterations in gene expression and their related pathways could give us hints for the development of new target-specific antiepileptic drugs that interfere with the progression of the disease in the juvenile age group

Dry eye and Meibomian gland dysfunction evaluation in sarcoidosis patients

PubMed: 338323422-s2.0-85104144117Purpose: To analyze the relation between Meibomian gland dysfunction, dry eye, and sarcoidosis. Materials and Methods: Twenty eyes of 10 sarcoidosis patients (Group 1) and 20 left eyes of 20 age-sex matched healthy volunteers (Group 2) were included. Presence of dry eye was evaluated with Schirmer 1 test, tear film break-up time (T-BUT), Oxford scale scoring, Ocular Surface Disease Index (OSDI) score assessments. A slit-lamp biomicroscope infrared filter (Topcon, SL-D701, IJssel, The Netherlands) was used to evaluate Meibomian glands. The drop-out ratio according to meibography was scored for each eyelid from grade 0 (no loss) through grade 3 (lost area >2/3 of the total Meibomian gland area). Results: Among dry eye tests mean Schirmer 1 and T-BUT values were lower and OSDI score was higher in Group 1 compared to Group 2 and the differences were statistically significant (p = 0.017, p = 0.039, p = 0.003, respectively). In addition, the upper, lower and total meiboscores were statistically significantly higher in Group 1 (p = 0.047, p = 0.003, p = 0.005, respectively). Conclusion: A significantly higher presence of dry eye and Meibomian gland drop out ratios was detected in sarcoidosis patients. It is important to monitor sarcoidosis patients for dry eye and Meibomian gland dysfunction and when detected, to treat adequately to prevent ocular surface damage. © The Author(s) 2021

TLR2 and TLR4 gene polymorphisms in Turkish vitiligo patients

WOS: 000312655900023PubMed ID: 22429552Background It has been shown that toll like receptors (TLR) may be involved in some inflammatory skin diseases such as psoriasis, atopic dermatitis. Vitiligo is an acquired pigmentation disorder of unknown aetiology. A number of genes playing a role in inflammatory response may be associated with development of vitiligo. Objectives To investigate whether there is an association between TLR 2 and TLR4 gene polymorphisms in Turkish patients with vitiligo. Methods A total of 100 patients (59 women and 41 men) with vitiligo and 100 controls (58 women and 42 men) were included in the study. The TLR2 gene Arg753Gln and TLR4 gene Asp299Gly and Thr399Ile polymorphisms were genotyped by using polymerase chain reaction and restriction fragment length polymorphism method. The data were analysed by MannWhitney U-test, chi-squared test and logistic regression analysis. Results Significant difference was found in the distribution of TLR2 Arg753Gln genotype and in the allele frequencies TLR2 753Gln between vitiligo patients and healthy subjects (P < 0.05). The distribution of TLR4 Asp299Gly genotype was significantly higher in the patient group (10%) than in the control group (%2) (P < 0.05). The TLR4 Thr399Ile distribution did not show any difference in both vitiligo and healthy groups. Conclusions Our findings suggest that Toll-like receptor 2 gene Arg753Gln and Toll-like receptor 4 Asp299Gly gene polymorphisms are associated with vitiligo susceptibility in Turkish patients